Prostate cancer is one of the most prevalent types of cancer in the U.S. and is among the leading causes of death in men of all races. One predictor of advanced prostate cancer and aggressive tumor behavior is the overexpression of the histone methyl transferase EZH2.
EZH2 functions in the nucleus by catalyzing the tri-methylation of histone H3 lysine 27 (H3K27) and mediates the silencing of target genes involved in essential cellular processes such as cell cycle regulation and cell identity. While EZH2 is also found in the cytoplasm of advanced cancer cells, its function here is not yet well understood. In the context of prostate cancer, dysregulated EZH2 represses the transcription of the tumor suppressor genes promoting tumor cell proliferation. Inhibition of EZH2 has been found to block prostate cancer cell growth, making EZH2 and valuable target for cancer therapy.
Epidemiological data suggests that eating cruciferous vegetables such as broccoli and cauliflower lowers risk of prostate cancer. It has been hypothesized that sulforaphane—a bioactive compound found in cruciferous vegetables—decreases prostate cancer cell proliferation. However, the mechanism by which sulforaphane exerts its effect is still under investigation. In other cancer cell types, treatment with sulforaphane has been found to decrease EZH2 levels in cells. The purpose of this study is to determine the effect of SFN on EZH2 expression in prostate cancer cells and identify potential mechanisms for the control of EZH2.
To answer these questions we looked at PC3 prostate cancer cells—a cancer line derived from human advanced malignant androgen-independent prostate tumor. PC3 cells were treated with 15mM sulforaphane or left untreated. Our study found that sulforaphane treatment caused a decrease in EZH2 expression compared to untreated cells. In contrast, sulforaphane treatment had no effect on H3K27me3 levels. It was also determined that the decrease in EZH2 expression was due to a decrease in cytoplasmic EZH2 leaving nuclear EZH2 largely unaffected.